| First Author | Wang L | Year | 2019 |
| Journal | Genes Dev | Volume | 33 |
| Issue | 11-12 | Pages | 641-655 |
| PubMed ID | 31048544 | Mgi Jnum | J:289183 |
| Mgi Id | MGI:6434603 | Doi | 10.1101/gad.323303.118 |
| Citation | Wang L, et al. (2019) ATDC is required for the initiation of KRAS-induced pancreatic tumorigenesis. Genes Dev 33(11-12):641-655 |
| abstractText | Pancreatic adenocarcinoma (PDA) is an aggressive disease driven by oncogenic KRAS and characterized by late diagnosis and therapeutic resistance. Here we show that deletion of the ataxia-telangiectasia group D-complementing (Atdc) gene, whose human homolog is up-regulated in the majority of pancreatic adenocarcinoma, completely prevents PDA development in the context of oncogenic KRAS. ATDC is required for KRAS-driven acinar-ductal metaplasia (ADM) and its progression to pancreatic intraepithelial neoplasia (PanIN). As a result, mice lacking ATDC are protected from developing PDA. Mechanistically, we show ATDC promotes ADM progression to PanIN through activation of beta-catenin signaling and subsequent SOX9 up-regulation. These results provide new insight into PDA initiation and reveal ATDC as a potential target for preventing early tumor-initiating events. |
